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Nucleic acid mediated activation of a short prokaryotic Argonaute immune system

Author

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  • Jithesh Kottur

    (Icahn School of Medicine at Mount Sinai
    Institute of Advanced Virology)

  • Radhika Malik

    (Icahn School of Medicine at Mount Sinai)

  • Aneel K. Aggarwal

    (Icahn School of Medicine at Mount Sinai)

Abstract

A short prokaryotic Argonaute (pAgo) TIR-APAZ (SPARTA) defense system, activated by invading DNA to unleash its TIR domain for NAD(P)+ hydrolysis, was recently identified in bacteria. We report the crystal structure of SPARTA heterodimer in the absence of guide-RNA/target-ssDNA (2.66 Å) and a cryo-EM structure of the SPARTA oligomer (tetramer of heterodimers) bound to guide-RNA/target-ssDNA at nominal 3.15–3.35 Å resolution. The crystal structure provides a high-resolution view of SPARTA, revealing the APAZ domain as equivalent to the N, L1, and L2 regions of long pAgos and the MID domain containing a unique insertion (insert57). Cryo-EM structure reveals regions of the PIWI (loop10-9) and APAZ (helix αN) domains that reconfigure for nucleic-acid binding and decrypts regions/residues that reorganize to expose a positively charged pocket for higher-order assembly. The TIR domains amass in a parallel-strands arrangement for catalysis. We visualize SPARTA before and after RNA/ssDNA binding and uncover the basis of its active assembly leading to abortive infection.

Suggested Citation

  • Jithesh Kottur & Radhika Malik & Aneel K. Aggarwal, 2024. "Nucleic acid mediated activation of a short prokaryotic Argonaute immune system," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-49271-4
    DOI: 10.1038/s41467-024-49271-4
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    1. Xiangkai Zhen & Biao Zhou & Zihe Liu & Xurong Wang & Heyu Zhao & Shuxian Wu & Zekai Li & Jiamin liang & Wanyue Zhang & Qingjian Zhu & Jun He & Xiaoli Xiong & Songying Ouyang, 2024. "Mechanistic basis for the allosteric activation of NADase activity in the Sir2-HerA antiphage defense system," Nature Communications, Nature, vol. 15(1), pages 1-13, December.

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